Outcomes of Patients With Classic Hodgkin Lymphoma Who Relapsed After Autologous Stem Cell Transplant

Abstract

Immune checkpoint inhibitors (ICIs) and brentuximab vedotin (BV) are novel agents for classic Hodgkin lymphoma, including relapse after autologous stem cell transplant (ASCT). However, their impact on survival post-ASCT relapse, in comparison with conventional therapy, is less known due to the lack of randomized controlled trials. Clinical characteristics and outcomes of 115 patients with relapse (or progression) after ASCT are studied. After a median follow-up of 8.59 years from post-ASCT relapse, the median progression-free survival (PFS) and overall survival (OS) were 0.91 and 5.07 years, respectively. Median lines of therapy after post-ASCT relapse was 2 (range, 1-12). The median PFS was not reached (NR) versus 1.11 versus 0.50 versus 0.85 versus 0.78 years (P = 0.006) and OS was NR versus 7.60 versus 3.08 versus 3.51 versus 3.17 years (P = 0.28) in patients first treated with ICIs versus BV versus investigational agents versus chemotherapy versus radiation therapy (RT). First-line treatment with novel agents (ie, ICIs and BV) was associated with superior outcomes compared with investigational agents and chemotherapy/RT with a median PFS of 1.65 versus 0.50 versus 0.79 years (P = 0.003) and a median OS of 7.60 versus 3.08 versus 3.32 years (P = 0.08). Regardless of lines of therapy, the treatment with ICIs had the most favorable outcome with a median PFS and OS of 3.98 and NR years, respectively. Allogeneic stem cell transplant (allo-SCT) was done in 23 patients (20%), and the median post-allo-SCT PFS and OS were 1.31 and 2.35 years, respectively. In conclusion, survival following post-ASCT relapse improves significantly when patients receive novel agents.

Graphical abstract

Figure 1.

PFS (A) and OS (B) of patients with cHL who relapsed after ASCT. ASCT = autologous stem cell transplant; cHL = classic Hodgkin lymphoma; OS = overall survival; PFS = progression-free survival.

Figure 2.

PFS (A and C) and OS (B and D) of patients with cHL that relapsed after ASCT by the first-line treatment. Investigational agents, everolimus, panobinostat, everolimus and panobinostat, everolimus and sorafenib, everolimus and lenalidomide, MDX-060 (iratumumab), MDX-060 plus gemcitabine, and tipifamib. ASCT = autologous stem cell transplant; BV = brentuximab vedotin; cHL = classic Hodgkin lymphoma; ICI = immune checkpoint inhibitor; OS = overall survival; PFS = progression-free survival; RT = radiation therapy.

Figure 3.

Sankey diagram that demonstrates the first-line and second-line management of RR cHL after post-ASCT relapse. Subsequent consolidative allo-SCT was done after: *BV (n = 4); **chemotherapy (n = 3); †BV (n = 1); ‡chemotherapy (n = 6). #2 patients had conditioning therapy and allo-SCT without preceding therapy (note 1 patient that had allo-SCT after post-ASCT relapse is not included in this diagram). ≠ and **refer to Table 2 footnote for detailed information of investigational agents and chemotherapy. ¥ and ‡ refer to Table 3 footnote for detailed information of investigational agents and chemotherapy. ± progressive disease (n = 13), pneumonitis (n = 1), allo-SCT related complication (n = 1), and unclear reason (n = 1). allo-SCT = allogeneic stem cell transplant; ASCT = autologous stem cell transplant; BV = brentuximab vedotin; cHL = classic Hodgkin lymphoma; ICI = immune checkpoint inhibitor; RR = relapsed or refractory; RT = radiation therapy.

Figure 4.

Kaplan-Meier curves of PFS (A) and OS (B) of patients with cHL who relapsed after ASCT by time to relapse (≤6 vs >6 mo) in the entire patient population and PFS (C) and OS (D) by time to relapse (≤6 vs >6 mo) in patients treated with novel therapy following post-ASCT relapse. ASCT = autologous stem cell transplant; cHL = classic Hodgkin lymphoma; OS = overall survival; PFS = progression-free survival.

Figure 5.

PFS (A) and OS (B) of patients with RR cHL by era at post-ASCT relapse. ASCT = autologous stem cell transplant; cHL = classic Hodgkin lymphoma; OS = overall survival; PFS = progression-free survival; RR = relapsed or refractory.